The transgenic core will provide injection services for the construction of transgenic mice by injection of DNA into fertilized oocytes and mice carrying targeted mutations by injection of ES cells into mouse blastocysts. It will also provide Center members with promoter/enhancer constructs for directing gene expression to different parts of the GI tract that have been developed in Dr. Gordon's laboratory. It will also provide consultations on embryonic stem cell manipulations. Established embryonic stem cell lines and fibroblast feeder cells will be supplied by an existing separate facility, Dr. Ley's stem cell core (Cancer Center), which will do the transfection and expansion of ES cells. This stem cell core does not provide injection services. The proposed facility will be developed from a mini-facility now operated by the Ornitz and Gordon laboratories. These laboratories have had a high level of success deriving transgenic, chimeric transgenic and knockout mice, so it is predicted that the facility will be efficient. The Transgenic Mouse and Stem Cell Core is located in a mouse barrier facility across the street from the medical center. There appears to be ample space for both the injection stations and no limitation on space for housing mice. The Core is equipped with three injection stations. Upon receiving funding, trained technicians from the Gordon and Orvitz laboratories will be recruited to work full time for the Core, with both technicians responsible for microinjections and animal husbandry.